Phthalic anhydride

85-44-9

Hazard Summary-Created in April 1992; Revised in January 2000

Exposure to phthalic anhydride may occur during its use as a chemical
intermediate in the plastics industry. The acute (short-term) effects
from exposure to phthalic anhydride in humans consists of irritation to
the eyes, respiratory tract, and skin, but no permanent injury is observed.
Chronic (long-term) effects observed in workers exposed to phthalic anhydride
included conjunctivitis, rhinitis, rhinoconjunctivitis, bronchitis, and
irritation of the skin and mucous membranes of the respiratory tract.
Animal studies indicate that chronic exposure to phthalic anhydride vapor
causes congestion, irritation, and injury to lung cells. No studies
are available on the reproductive, developmental, or carcinogenic effects
of phthalic anhydride in humans. EPA has not classified phthalic
anhydride for carcinogenicity.

Uses

Phthalic anhydride is an important chemical intermediate in the plastics
industry from which are derived numerous phthalate esters that function
as plasticizers in synthetic resins. Phthalic anhydride itself
is used as a monomer for synthetic resins such as glyptal, the alkyd
resins, and the polyester resins. (1)

Phthalic anhydride is also used as a precursor of anthraquinone,
phthalein, rhodamine, phthalocyanine, fluorescein, and xanthene dyes.
(1)

Sources and Potential Exposure

Exposure to phthalic anhydride may occur during the manufacture of
phthalate-derived products. (1)

It has been suggested that exposure to phthalic anhydride may occur
from the use of plastics from which phthalate plasticizers are leached,
specifically certain medical plastics such as blood bags, plastic syringes,
and plastic tubing. (1)

Phthalate esters have been identified as environmental pollutants.
(1)

Assessing Personal Exposure

There is no known medical test available to determine whether someone
has been exposed to phthalic anhydride. (2)

Health Hazard Information

Acute Effects:

Phthalic anhydride is irritating to the eyes, respiratory tract,
and the skin in humans, but no permanent injury is observed. Since
phthalic anhydride has no effect on dry skin, but burns wet skin, it
has been suggested that the actual irritant is phthalic acid, which
is formed on contact with water. (2)

Conjunctivitis, rhinitis, rhinoconjunctivitis, bronchitis, and irritation
of the skin and mucous membranes of the respiratory tract have been
observed in workers exposed to phthalic anhydride. Other effects
observed in workers chronically exposed to phthalic anhydride were occasional
bloody sputum, emphysema, lower blood pressure, and minor signs of central
nervous system (CNS) excitation. (1,2,9)

Decreased body weight, increased incidence of lung and kidney lymphocytosis,
bile duct inflammation, adrenal atrophy, and mineralization of the thalmus
were reported in mice exposed to phthalic anhydride in the diet. (1,4)

EPA has calculated a provisional Reference Concentration (RfC)
of 0.12 milligrams per cubic meter (mg/m3) for phthalic anhydride
based on respiratory effects in humans. The RfC
is an estimate (with uncertainty spanning perhaps an order of magnitude)
of a continuous inhalation exposure to the human population (including
sensitive subgroups) that is likely to be without appreciable risk of
deleterious noncancer effects during a lifetime. It is not a direct
estimator of risk but rather a reference point to gauge the potential
effects. At exposures increasingly greater than the RfC,
the potential for adverse health effects increases. Lifetime exposure
above the RfC does not imply
that an adverse health effect would necessarily occur. The provisional
RfC is a value that has had
some form of Agency review, but it does not appear on IRIS system. (5)

EPA has established a Reference Dose (RfD)
of 2.0 milligrams per kilogram body weight per day (mg/kg/d) for phthalic
anhydride based on lung and kidney effects in mice. (4)

EPA has high confidence in the study on which the RfD
is based because the study is a well-designed feeding study in two species
that defines a no-observed-adverse-effect level (NOAEL)
and lowest-observed-adverse-effect level (LOAEL);
medium confidence in the database because teratogenicity has not been
tested adequately; and, consequently, medium confidence in the RfD
because of the lack of reproductive toxicity data. (4)

Reproductive/Developmental Effects:

No studies regarding reproductive or developmental effects in humans
were available.

Phthalic anhydride was reported to be teratogenic in mice following
intraperitoneal injection. (4)

Decreased spermatozoa motility time was reported in one study in
which male rats were exposed via inhalation. (9)

Cancer Risk:

No studies were available on the carcinogenic effects of phthalic
anhydride in humans.

A bioassay of phthalic anhydride for possible carcinogenicity was
conducted by administering phthalic anhydride in feed to groups of male
and female rats and mice. It was observed that no tumors occurred
in the rats or mice of either sex at incidences that could be clearly
related to the administration of phthalic anhydride. (1)

Health Data from Inhalation Exposure

ACGIH TLV--American Conference of Governmental and Industrial
Hygienists' threshold limit value expressed as a time-weighted average;
the concentration of a substance to which most workers can be exposed
without adverse effect. NIOSH REL--National Institute of Occupational Safety and Health's
recommended exposure limit; NIOSH-recommended exposure limit for an 8-
or 10-h time-weighted-average exposure and/or ceiling. NIOSH IDLH -- NIOSH's immediately dangerous to life or health concentration;
NIOSH recommended exposure limit to ensure that a worker can escape from
an exposure condition that is likely to cause death or immediate or delayed
permanent adverse health effects or prevent escape from the environment.
OSHA PEL--Occupational Safety and Health Administration's permissible
exposure limit expressed as a time-weighted average; OSHA allowable level
in workplace air averaged over an 8-h shift.

The health and regulatory values cited in this factsheet were obtained
in December 1999.aHealth numbers are toxicological numbers
from animal testing or risk assessment values developed by EPA. bRegulatory numbers are values that have been
incorporated in Government regulations, while advisory numbers are nonregulatory
values provided by the Government or other groups as advice. OSHA numbers
are regulatory, whereas NIOSH and ACGIH numbers are advisory.

J.E. Amoore and E. Hautala. Odor as an aid to
chemical safety: Odor thresholds compared with threshold limit values
and volatilities for 214 industrial chemicals in air and water dilution.
Journal of Applied Toxicology, 3(6):272-290. 1983.

National Institute for Occupational Safety and
Health (NIOSH). Pocket
Guide to Chemical Hazards. U.S. Department of Health and
Human Services, Public Health Service, Centers for Disease Control and
Prevention. Cincinnati, OH. 1997.